Open AccessO-linked β-N-acetylglucosamine transferase plays an essential role in heart development through regulating angiopoietin-1
Author(s) -
Yongxin Mu,
Haiqing Yu,
Taihu Wu,
Jianlin Zhang,
Sylvia M. Evans,
Ju Chen
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008730
Subject(s) - heart development , biology , transferase , microbiology and biotechnology , knockout mouse , angiopoietin , function (biology) , medicine , enzyme , embryonic stem cell , biochemistry , cancer research , gene , vegf receptors , vascular endothelial growth factor
O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only enzyme catalyzing O-GlcNAcylation. Although it has been shown that OGT plays an essential role in maintaining postnatal heart function, its role in heart development remains unknown. Here we showed that loss of OGT in early fetal cardiomyocytes led to multiple heart developmental defects including hypertrabeculation, biventricular dilation, atrial septal defects, ventricular septal defects, and defects in coronary vessel development. In addition, RNA sequencing revealed that Angiopoietin-1, required within cardiomyocytes for both myocardial and coronary vessel development, was dramatically downregulated in cardiomyocyte-specific OGT knockout mouse hearts. In conclusion, our data demonstrated that OGT plays an essential role in regulating heart development through activating expression of cardiomyocyte Angiopoietin-1.